From our continuing studies on the synthesis and conformation of the luteinizing hormone-releasing hormone (LH-RH) analogs, the following conclusions can be made: 1. The in vitro agonist activity of the three newly synthesized analogs of LH-RH ranges from 0.0001% through 0.006% to 2-3%. 2. The nmr studies of the 15N analogs suggest that there are two possible conformers for the (D-Ala6) LH-RH analog: a C7 ring or a Beta-turn involving the amino acid residues 4-7. This conformational flexibility may explain the enhanced biological activity of this analog. We are also carrying out the synthesis of a retro-inverso modified Ala5-somatostatin analog. This modification makes all three postulated cleavage sites fall within the modifid region while leaving intact the part essential for biological activity of this hormone. The biological activity and metabolism of this analog will be studied.